Diabetes mellitus is associated with degenerative changes in the cardio-vascular system. The etiology of these vascular changes remain uncertain and is controversial. Studies of the accelerated vascular changes in young diabetic subjects may lead to a better understanding of the more insidious development of the serious vascular diseases commonly observed in the general population. The study proposed is designed to continue long term longitudinal studies of children with chemical and overt diabetes to determine the interrelationship between early recognition and metabolic control of the diabetes and the time of appearance and rate of progression of the micro-vascular changes known to occur with the disease. Vascular status is being determined in both normal and diabetic children of comparable ages by measuring with the electron microscope the thickness of the capillary basement membranes from muscle biopsies. Fluorescein retinal photography also is being performed on selected subjects to correlate the degree of thickness of the capillary basement membrane in the striated muscles of the thigh with the early vascular changes in the eye grounds. These retinal changes often begin to appear 10 to 20 years after the onset of clinical (overt) diabetes. We believe these observations to be important as the retinal changes are invariably the first definite clinical signs of vascular disease in patients with juvenile diabetes. In this new proposal, diabetic subjects from two clinics (Columbia, Mo. and Pittsburgh, Pa.) will be studied to provide two comparable groups of subjects except for the degree of conrol of their diabetes. Additional data are necessary from both normal and diabetic subjects in order to provide a sufficient number of observations to verify statistically if there is a definite relationship between the degree of control of the disease and rate of progression of the micro-vascular changes.